Eleutherlenes A–D, Diverse Types of Naphthalene Derivatives with Anti-inflammatory Activity from Eleutherine bulbosa

作者：Yuan Gao, Ying Li, Jun‐Su Zhou, Zhixiang Xie, Pei‐Qian Wu, Qing Mu, Bin Zhou, Jian‐Min Yue · 发表于：Organic Letters · 年份：2025 · DOI：10.1021/acs.orglett.4c04798 · 被引用次数：9 · 研究领域：Bioactive Compounds and Antitumor Agents、Marine Sponges and Natural Products、Traditional and Medicinal Uses of Annonaceae

Eleutherlene A ( 1 ), an unprecedented carbon skeleton featuring an aryl-fused 6-methyl-2,7-dioxabicyclo[3.2.1]octane unit, and eleutherlene B ( 2 ), a naphthoquinone derivative with interesting ring fusion of an α,β-unsaturated γ-lactam and a tetrahydropyran moiety, along with two novel naphthoquinone alkaloids, eleutherlenes C ( 3 ) and D ( 4 ), were isolated from Eleutherine bulbosa and identified. Their structures were elucidated by spectroscopic analyses along with computer-assisted structure elucidation, including ACD/Structure Elucidator and computational calculations and X-ray crystal diffraction. A plausible biosynthetic route for 1 and 2 was proposed. Compound 1 showed significant anti-inflammatory activity with respect to the inhibition of pro-inflammatory mediators NO, IL-1β, iNOS, and COX-2. Mechanistically, compound 1 inhibited the inflammatory response by suppressing NF-κB/MAPK and activating the Nrf2/Keap1 signaling pathway in LPS-induced RAW 264.7 cells.